title: Lack of effects of hyperglycemia on the disposal of 3-hydroxybutyrate in insulin-dependent diabetic patients.
abstract: There is evidence that hyperketonemia in insulin-dependent diabetes may be aggravated by a decreased disposal rate for ketone bodies. To test the hypothesis that this decrease may be induced by concomitant hyperglycemia through substrate competition at the acetyl-CoA level, 5 young insulin-dependent diabetic subjects received at 2-h iv infusion of 0.9 mmol 3-hydroxybutyrate.kg-1.h-1 at clamped 1. euglycemia (5 mmol/l) and 2. hyperglycemia (11 mmol/l) on separate occasions. To ensure similar metabolic conditions, a low-dose hyperinsulinemic euglycemic clamp was performed during the 5 h preceding the actual studies. Substrate fluxes in muscle were assessed through the forearm technique. The glucose infusion rate was 4.9 and 2.9 mg.kg-1.min-1, and the forearm arteriovenous difference for glucose was 0.72 during hyperglycemia and 0.39 mmol/l (p less than 0.05), during euglycemia. Hyperglycemia did not affect circulating levels of free insulin, glucagon, non-esterified fatty acids, 3-hydroxybutyrate (hyperglycemia: 665, euglycemia: 770 mumol/l, p greater than 0.05) or acetoacetate, nor forearm uptake of 3-hydroxybutyrate (hyperglycemia, 152, euglycemia: 168 mumol/l, p greater than 0.05). In conclusion, our results do not suggest any inhibitory role for hyperglycemia in the disposal of ketone bodies. In as much as extrapolation from the present well insulinized state is appropriate, the data indicate that alternative mechanisms may be involved in the observed impairment of ketone body clearance in hyperketonemic insulin-dependent diabetic patients.
authors.affiliation: 2nd University Clinic of Internal Medicine, Aarhus Kommunehospital, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Møller
authors.forename: J O
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: J
authors.initials: J
authors.lastname: Møller
authors.forename: L
authors.initials: L
authors.lastname: Orskov
authors.forename: N
authors.initials: N
authors.lastname: Pørksen
authors.forename: K G
authors.initials: KG
authors.lastname: Alberti
authors.forename: O
authors.initials: O
authors.lastname: Schmitz
mesh_terms: D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000097:blood; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood* / Q000493:pharmacokinetics; D006943:Hyperglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood; D008297:Male
chemical_list: D000090:Acetoacetates; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; C016635:acetoacetic acid; D020155:3-Hydroxybutyric Acid